The expanded FindCore method for identification of a core atom set for assessment of protein structure prediction

Proteins. 2014 Feb;82 Suppl 2(0 2):219-30. doi: 10.1002/prot.24490.

Abstract

Maximizing the scientific impact of NMR-based structure determination requires robust and statistically sound methods for assessing the precision of NMR-derived structures. In particular, a method to define a core atom set for calculating superimpositions and validating structure predictions is critical to the use of NMR-derived structures as targets in the CASP competition. FindCore (Snyder and Montelione, Proteins 2005;59:673-686) is a superimposition independent method for identifying a core atom set and partitioning that set into domains. However, as FindCore optimizes superimposition by sensitively excluding not-well-defined atoms, the FindCore core may not comprise all atoms suitable for use in certain applications of NMR structures, including the CASP assessment process. Adapting the FindCore approach to assess predicted models against experimental NMR structures in CASP10 required modification of the FindCore method. This paper describes conventions and a standard protocol to calculate an "Expanded FindCore" atom set suitable for validation and application in biological and biophysical contexts. A key application of the Expanded FindCore method is to identify a core set of atoms in the experimental NMR structure for which it makes sense to validate predicted protein structure models. We demonstrate the application of this Expanded FindCore method in characterizing well-defined regions of 18 NMR-derived CASP10 target structures. The Expanded FindCore protocol defines "expanded core atom sets" that match an expert's intuition of which parts of the structure are sufficiently well defined to use in assessing CASP model predictions. We also illustrate the impact of this analysis on the CASP GDT assessment scores.

Keywords: CASP; NMR; RMSD; protein structure; superimposition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Computational Biology / methods*
  • Models, Molecular*
  • Models, Statistical
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation*
  • Proteins / chemistry*
  • Software*

Substances

  • Proteins